A Study of Asacol Absorption, Metabolism and Excretion in Children and Adolescents With Ulcerative Colitis.

NCT ID: NCT00254618

Last Updated: 2013-04-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-10-31

Study Completion Date

2008-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this randomized, open-label, parallel-group study is to determine how the body absorbs and eliminates mesalamine following administration of either 30 mg/kg/day, 60 mg/kg/day or 90 mg/kg/day as 400 mg delayed-release tablets given every 12 hours of 28 days to children and adolescents with active ulcerative colitis.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Ulcerative colitis is a type of inflammatory bowel disease characterized by diffuse, continuous inflammation of the colon. Recent estimates suggest that approximately 17,000 children between 5 and 17 years of age in the U.S. are diagnosed with ulcerative colitis. Estimates of average age at onset in children vary, although 80-90% of patients are 9 years of age or older when symptoms develop.

Asacol is a delayed-release tablet formulation designed to deliver mesalamine (also known as mesalazine) at a pH ≥ 7.0. This property results in release of the drug in the terminal ileum and beyond. Physiologic factors such as the pH of the surrounding medium, transit times in the intestinal regions of interest, and the rate and extent of absorption and metabolism govern Asacol drug release and delivery, which in turn influence the pharmacokinetic profile of the delivered drug. These physiologic factors and their effect on Asacol pharmacokinetics have been studied in adults, but corresponding studies in children have not been performed. However, relevant studies describing the gastrointestinal pH; transit times; and pharmacokinetic aspects of drug absorption, metabolism, and excretion in pediatric patients (relative to adults) provide reasons to expect that the performance characteristics of Asacol in the pediatric population will be similar to those measured in adults.

In a compassionate-use study that included 66 children between the ages of 3 and 16 years, the safety profile of long-term mesalamine therapy (10 to 93 mg/kg/day) was similar to that observed among adult patients enrolled in the study. In addition, in a retrospective study of 732 pediatric patients with inflammatory bowel disease (153 of whom were treated with mesalamine), D'Agata, et al. concluded that mesalamine was safe and well tolerated when used long term at doses ranging from 13 to 111 mg/kg/day. Although few clinical studies of mesalamine have been performed in children, pediatric gastroenterologists use mesalamine to treat children with inflammatory bowel disease, and doses higher than those proposed for this study (up to 100 mg/kg/day) have been recommended.

This study will provide information about the pharmacokinetics of mesalamine and its major metabolite in children being treated with Asacol for mildly to moderately active ulcerative colitis. It was designed to meet the expectations outlined in a Written Request issued by the FDA, as well as regulatory requirements to study the weight-based equivalent of 4.8 g/day. The age-appropriate dose formulation, the 400 mg tablet, will be used, and patients will be dosed every 12 hours, since this regimen is considered more convenient for pediatric patients and their parents.

During this open-label, randomized, 4-week parallel-group study in pediatric patients, patients will be stratified by age (5-8 years and 9-17 years), and randomly assigned to one of 3 dose levels (30 mg/kg/day, 60 mg/kg/day, and 90 mg/kg/day) in the manner described in Section 3.5.1. Patients weighing less than 20 kg will not be assigned to the 30 mg/kg group, and patients weighing more than 60 kg will not be assigned to the 90 mg/kg group, due to dosing concerns. A total of 48 patients will be enrolled (8/treatment group/age stratum), with the expectation that 36 (6/treatment group/age stratum) will complete.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Ulcerative Colitis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

30 mg

30 mg/kg/day mesalamine

Group Type EXPERIMENTAL

mesalamine

Intervention Type DRUG

oral tablet, 30 mg mesalamine/day for 28 days

60 mg

60 mg/kg/day mesalamine

Group Type EXPERIMENTAL

mesalamine

Intervention Type DRUG

oral tablet, 60 mg mesalamine/day for 28 days

90 mg

90 mg/kg/day mesalamine

Group Type EXPERIMENTAL

mesalamine

Intervention Type DRUG

oral tablet, 90 mg mesalamine/day for 28 days

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

mesalamine

oral tablet, 30 mg mesalamine/day for 28 days

Intervention Type DRUG

mesalamine

oral tablet, 60 mg mesalamine/day for 28 days

Intervention Type DRUG

mesalamine

oral tablet, 90 mg mesalamine/day for 28 days

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Patients are eligible to participate in the study if they have/are:

1. male or female between the ages of 5 and 17 years, inclusive, at the time of the first dose of study medication
2. mildly to moderately active ulcerative colitis (either newly- or previously-diagnosed), as confirmed by their physician, for which mesalamine would be used as part of their normal treatment
3. generally in good health (other than the diagnosis of ulcerative colitis), based on medical history, physical examination, and screening laboratory results
4. able to swallow Asacol tablets (400 mg marketed US formulation)
5. a body weight no less than 16 kg and no more than 90 kg
6. able and willing to participate in the study and follow study procedures, as evidenced by providing assent and having a parent/guardian-signed written informed consent.

Exclusion Criteria

Patients will be excluded from the study if they have/are:

1\. a history of cancer 2. a history of intestinal surgery or malabsorption 3. a history of renal insufficiency 4 a history of allergy or hypersensitivity to salicylates or aminosalicylates 5. evidence of clinically significant organic or psychiatric disease on medical history or physical examination that, in the Investigator's opinion, would prevent the patient from completing the study or would jeopardize the patient's safety 6. a creatinine clearance of \< or =30 mL/minute at screening, estimated by serum creatinine using the Traub \& Johnson equation for calculating pediatric creatinine clearance.

7\. a screening BUN or creatinine value that is \>1.5 times the upper limit of normal, or liver function tests that are \>2 times the upper limit of normal 8. any other screening laboratory test values that the Investigator or Sponsor considers clinically significant that would impact the outcome of the study or the safety of the patient 9. using proton pump inhibitors or antacids 10. pregnant (post-menarchal female patients should be made aware that pregnancy testing will occur during the study, and that if they are sexually active they must take appropriate steps to ensure they do not become pregnant during the study) 11. a positive urine screen for drugs of abuse 12. participated in another clinical trial involving active intervention within 30 days prior to randomization.
Minimum Eligible Age

5 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Warner Chilcott

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

William Aronstein, MD, PhD

Role: STUDY_DIRECTOR

Procter and Gamble

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Research Site

Birmingham, Alabama, United States

Site Status

Research Site

Mobile, Alabama, United States

Site Status

Research Site

Costa Mesa, California, United States

Site Status

Research Site

San Diego, California, United States

Site Status

Research Site

San Francisco, California, United States

Site Status

Research Site

Gainesville, Florida, United States

Site Status

Research Site

Jacksonville, Florida, United States

Site Status

Research Site

Park Ridge, Illinois, United States

Site Status

Research Site

Baltimore, Maryland, United States

Site Status

Research Site

Boston, Massachusetts, United States

Site Status

Research Site

Detroit, Michigan, United States

Site Status

Research Site

Omaha, Nebraska, United States

Site Status

Research Site

Morristown, New Jersey, United States

Site Status

Research Site

Buffalo, New York, United States

Site Status

Research Site

Cincinnati, Ohio, United States

Site Status

Research Site

Cleveland, Ohio, United States

Site Status

Research Site

Portland, Oregon, United States

Site Status

Research Site

Greenville, South Carolina, United States

Site Status

Research Site

Dallas, Texas, United States

Site Status

Research Site

Houston, Texas, United States

Site Status

Research Site

Pasadena, Texas, United States

Site Status

Research Site

Seattle, Washington, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2005018

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.